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        Divergent reprogramming routes lead to alternative stem-cell states

        Tonge, Peter D.,Corso, Andrew J.,Monetti, Claudio,Hussein, Samer M. I.,Puri, Mira C.,Michael, Iacovos P.,Li, Mira,Lee, Dong-Sung,Mar, Jessica C.,Cloonan, Nicole,Wood, David L.,Gauthier, Maely E.,Korn, Nature Publishing Group, a division of Macmillan P 2014 Nature Vol.516 No.7530

        Pluripotency is defined by the ability of a cell to differentiate to the derivatives of all the three embryonic germ layers: ectoderm, mesoderm and endoderm. Pluripotent cells can be captured via the archetypal derivation of embryonic stem cells or via somatic cell reprogramming. Somatic cells are induced to acquire a pluripotent stem cell (iPSC) state through the forced expression of key transcription factors, and in the mouse these cells can fulfil the strictest of all developmental assays for pluripotent cells by generating completely iPSC-derived embryos and mice. However, it is not known whether there are additional classes of pluripotent cells, or what the spectrum of reprogrammed phenotypes encompasses. Here we explore alternative outcomes of somatic reprogramming by fully characterizing reprogrammed cells independent of preconceived definitions of iPSC states. We demonstrate that by maintaining elevated reprogramming factor expression levels, mouse embryonic fibroblasts go through unique epigenetic modifications to arrive at a stable, Nanog-positive, alternative pluripotent state. In doing so, we prove that the pluripotent spectrum can encompass multiple, unique cell states.

      • SCOPUSSCIEKCI등재

        Neuroprotective Effects of Quetiapine on Neuronal Apoptosis Following Experimental Transient Focal Cerebral Ischemia in Rats

        Yilmaz, Muhammet Bahadir,Tonge, Mehmet,Emmez, Hakan,Kaymaz, Figen,Kaymaz, Memduh The Korean Neurosurgical Society 2013 Journal of Korean neurosurgical society Vol.54 No.1

        Objective : This study was undertaken in the belief that the atypical antipsychotic drug quetiapine could prevent apoptosis in the penumbra region following ischemia, taking into account findings that show 5-hydroxytryptamine-2 receptor blockers can prevent apoptosis. Methods : We created 5 groups, each containing 6 animals. Nothing was done on the K-I group used for comparisons with the other groups to make sure adequate ischemia had been achieved. The K-II group was sacrificed on the 1st day after transient focal cerebral ischemia and the K-III group on the 3rd day. The D-I group was administered quetiapine following ischemia and sacrificed on the 1st day while the D-II group was administered quetiapine every day following the ischemia and sacrificed on the 3rd day. The samples were stained with the immunochemical TUNEL method and the number of apoptotic cells were counted. Results : There was a significant difference between the first and third day control groups (K-II/K-III : p=0.004) and this indicates that apoptotic cell death increases with time. This increase was not encountered in the drug groups (D-I/D-II : p=1.00). Statistical analysis of immunohistochemical data revealed that quetiapine decreased the apoptotic cell death that normally increased with time. Conclusion : Quetiapine is already in clinical use and is a safe drug, in contrast to many substances that are used to prevent ischemia and are not normally used clinically. Our results and the literature data indicate that quetiapine could help both as a neuronal protector and to resolve neuropsychiatric problems caused by the ischemia in cerebral ischemia cases.

      • SCISCIESCOPUS

        Genome-wide characterization of the routes to pluripotency

        Hussein, Samer M. I.,Puri, Mira C.,Tonge, Peter D.,Benevento, Marco,Corso, Andrew J.,Clancy, Jennifer L.,Mosbergen, Rowland,Li, Mira,Lee, Dong-Sung,Cloonan, Nicole,Wood, David L. A.,Munoz, Javier,Midd Nature Publishing Group, a division of Macmillan P 2014 Nature Vol.516 No.7530

        Somatic cell reprogramming to a pluripotent state continues to challenge many of our assumptions about cellular specification, and despite major efforts, we lack a complete molecular characterization of the reprograming process. To address this gap in knowledge, we generated extensive transcriptomic, epigenomic and proteomic data sets describing the reprogramming routes leading from mouse embryonic fibroblasts to induced pluripotency. Through integrative analysis, we reveal that cells transition through distinct gene expression and epigenetic signatures and bifurcate towards reprogramming transgene-dependent and -independent stable pluripotent states. Early transcriptional events, driven by high levels of reprogramming transcription factor expression, are associated with widespread loss of histone H3 lysine 27 (H3K27me3) trimethylation, representing a general opening of the chromatin state. Maintenance of high transgene levels leads to re-acquisition of H3K27me3 and a stable pluripotent state that is alternative to the embryonic stem cell (ESC)-like fate. Lowering transgene levels at an intermediate phase, however, guides the process to the acquisition of ESC-like chromatin and DNA methylation signature. Our data provide a comprehensive molecular description of the reprogramming routes and is accessible through the Project Grandiose portal at http://www.stemformatics.org.

      • SCOPUSKCI등재
      • KCI등재
      • KCI등재

        Cytological, genetic, and proteomic analysis of a sesame (Sesamum indicum L.) mutant Siyl‑1 with yellow–green leaf color

        Tong‑Mei Gao,Shuang‑Ling Wei,Jing Chen,Yin Wu,Feng Li,Li‑Bin Wei,Chun Li,Yan‑Juan Zeng,Yuan Tian,Dong‑Yong Wang,Hai‑Yang Zhang 한국유전학회 2020 Genes & Genomics Vol.42 No.1

        Background Both photosynthetic pigments and chloroplasts in plant leaf cells play an important role in deciding on the photosynthetic capacity and efficiency in plants. Systematical investigating the regulatory mechanism of chloroplast development and chlorophyll (Chl) content variation is necessary for clarifying the photosynthesis mechanism for crops. Objective This study aims to explore the critical regulatory mechanism of leaf color mutation in a yellow–green leaf sesame mutant Siyl-1. Methods We performed the genetic analysis of the yellow-green leaf color mutation using the F2 population of the mutant Siyl-1. We compared the morphological structure of the chloroplasts, chlorophyll content of the three genotypes of the mutant F2 progeny. We performed the two-dimensional gel electrophoresis (2-DE) and compared the protein expression variation between the mutant progeny and the wild type. Results Genetic analysis indicated that there were 3 phenotypes of the F2 population of the mutant Siyl-1, i.e., YY type with light-yellow leaf color (lethal); Yy type with yellow-green leaf color, and yy type with normal green leaf color. The yellowgreen mutation was controlled by an incompletely dominant nuclear gene, Siyl-1. Compared with the wild genotype, the chloroplast number and the morphological structure in YY and Yy mutant lines varied evidently. The chlorophyll content also significantly decreased (P < 0.05). The 2-DE comparison showed that there were 98 differentially expressed proteins (DEPs) among YY, Yy, and yy lines. All the 98 DEPs were classified into 5 functional groups. Of which 82.7% DEPs proteins belonged to the photosynthesis and energy metabolism group. Conclusion The results revealed the genetic character of yellow-green leaf color mutant Siyl-1. 98 DEPs were found in YY and Yy mutant compared with the wild genotype. The regulation pathway related with the yellow leaf trait mutation in sesame was analyzed for the first time. The findings supplied the basic theoretical and gene basis for leaf color and chloroplast development mechanism in sesame.

      • 사랑의 意識空間 統合構造 : William Blake 論(4) William Blake's Poetry(4)

        姜通源 제주대학교 1985 논문집 Vol.22 No.2

        Willaim Blake has been called "the first English Romantic." He was also known as a mystic in history of English literature, and so he lived much of his time among his world of vision and spiritual communications. Therefore, some of his verse is not only hard to comprehend but also ambiguous to read because of symbolic characteristic, but the bulk of his poetry is as delightfully lyric and imaginative as that of any of the romantic poets. His best poetry is contained in the two collections ; Songs of Innocence and Songs of Experience. And yet we can also find Blaek's early poetry, simple and emotional, composed in his teens. It is Poetical Sketches juvenilia, of the first collection of his works. The juvenilia marks a turning point between the eighteenth century literature of Neoclassicism and the nineteenth century literature of Romanticism. The epochal early works are subjective and imaginative in his approach to the world of aesthetics from the objective expressions and rational statements. There appears some odes with other works in Blake's juvenilia, Poetical Sketches. They are odes of seasonal materials and concerning with the Muses, and the other works are songs entitled "Song" of the same theme of love. Then the present writer argued already about the seasonal problems and the problems of the Muses in the paper of "William Blake's Poetry"(2?3). Now, in this paper, the present writer has dealt with the questions of love in poetry, mating the three songs among them the subject of criticism. And also this paper has been a study of Blake's poetic thoughts, feelings, and symbolic images expressed in his love poems, in connection with the integrated space-stucture of love consciousness, laying special emphasis on the poems : “Song”(Love and harmony combine), "Song"(I love the jocund dance), and "Song"(Fresh from the dewy hill, the merry year).

      • 김운용 이후 스포츠지도자 양성의 문제 탐색

        양통일,이재봉 한국스포츠리서치 2005 한국 스포츠 리서치 Vol.16 No.2

        From the results of this research as to the exemplary model of Un-Yong Kim's question of sports and power deviation were following conclusions by investigating the real identification of Un-Yong Kim as a person who is regarded as a self-made man in the world sport industry, and by coping with those problems in the P.E. and sport coming up right after his retirement and the problem of how we can turn out sport leaders who can be spokesmen for Korea P.E. and sports and are capable and competitive in the world. 1. For a short-term period, it is necessary that the Ministry of Culture & Tourism should form a sport human resource pool for international committees in the Korea Olympic Committee as a short-term measure and that it should devise a mid and long term measure to take a proper step for training sport professionals for the diplomatic service and thus that a sufficient government budget is required for all these projects. 2. Through its influence and the mass media, the national government needs to support Korea sport leaders and athletes who are presently working in foreign countries, and also it should establish an extended policy for supporting civil sector sport exchanges with overseas countries. 3. It is necessary to improve the disposition of leaders for the image reform in the sport industry of the country, and the people themselves in the P.E. and sport need to secure the capability of attaining the influential power for the systemic and bureaucratic movements. 4. The national government and responsible institutions related with the P.E. and sport are to collect public opinions in a nation-broad dimension. 5. The continuance of authoritarianism regimes in our society have reinforced authoritative implicitness assertively for public interest, and it is true that it caused a tendency of regarding even the public good and interests as antagonism and suppression against the society. Accordingly, it is necessary to rediscovering the supplementary relation of personal interest with that of the public, and to seek for models that can produce moral leaders in the P.E. and sport, pursuing the ideals for the public and the personal harmoniously.

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